Our Peptide Chemistry team, in collaboration with scientists at Merck and Co., reported on the design, synthesis and characterization of potent and stable peptides able to inhibit the binding of NRF2-MAFG heterodimeric transcription factor to Antioxidant Response Element (ARE) DNA sequence. These peptides may provide interesting starting points for the development of therapeutic agents for tumors with a dysregulated NRF2-dependent pathway. Highly complex peptide heterodimers of long NRF2 and MAFG fragments exploiting various heterodimerization chemistries were generated based on a novel hybrid homology model. The model was built from the published crystal structure of the homodimeric MAFG/MAFG complex on DNA and the NMR structure of the NRF2 N-terminal loops of the DNA-binding domain. This type of strategy could prove useful to identify inhibitors of transcription factors beyond NRF2.